Acquired immune deficiency syndrome (AIDS) has emerged as the most serious disease discovered in recent times. AIDS patients, whose immunity is drastically reduced by infection by the human immune deficiency virus (HIV) get more serious diseases with rapid fatalistic consequences, by several opportunistic infections. Most serious among these infections are those caused by Mycobacterium aviuim complex (MAC), with which this research project is concerned. The principal invesigator (PI) established that the beige mouse (C57B1/bgJ/bgJ) to be the most susceptibel mouse strain among several strains studied, to MAC infections. Beige mice get advanced acute MAC disease, with associated mortality, following intravenous, aerogenic, intraperitoneal, oral and intrarectal challenges, with evidence of increased disease following mulitple challenges over single exposures. Of particular relevance to the lifestyle of homosexual men, the vast majority of AIDS patients, are the single and multiple challenges via the intrarectal route. The PI had also shown that beige mice are similar to AIDS patients in many immunopathological features. Using single and multiple, intravenous and intrarectal challenges with virulent MAC, containing drug resistance markers, of beige and the parent C57B1/6 mice, this investigation explores why only 3 serotypes 1,4 and 8, among the 31 serotypes occurring in the evnironment are causing MAC disease in AIDS patients. Likewise, these studies inquire why all the MAC strains isolated from AIDS patients possessed plasmids, while only 5% of the environmental strains do so. Developing on the known and established immunobiological features of beige mice, these investigations examine why this mouse strain is most susceptible to MAC challenges. Absence of natural killer (NK) cell activity in beige mice is given great consideration in these studies. Finally, this project envisages several immunomodulations of the beige mice using immunosuppressive and immunopotentiating agents, specifically directed against NK cell activity. It is hoped that many of these studies will give important leads on the immunopathology of MAC disease in AIDS and immunotherapy of AIDS patients against MAC disease.